The date of birth was discovered by the Florentine chronicler Antonio Pucci (1348-1388 circa), who places his death in 1337 (1336 Florentine style) at the age of seventy.

In the last decade of the century, Giotto is employed at Assisi in painting the cycle of frescoes depicting the stories of St. Francis. The St. Francis cycle at Assisi is one of history's most clamorous cases of an artistic masterpiece where there is a total lack of dependable dates about when they were done and the artist (or artists) who did them. Identifying the artist is one of the most complicated riddles in art history.
The first mention of Giotto's work at Assisi comes from Riccobaldo da Ferrara. But it is Ghiberti (1450 ca) who first maintains that Giotto "painted almost all the lower part" in the Church of the Asciesi, of the Minorite order. The only information about who commissioned it is given by Giorgio Vasari in the second edition of his Lives of the Artists (1568). There he affirms that the cycle was painted when Fra Giovanni da Murro (1296-1304) was General of the Franciscan Order. But this dating has been contested by many scholars who put these frescoes earlier, during the pontificate of Nicholas IV, which means in the early 1290s. We know that, in the main Assisi work sites, starting with The Stories of Isaac, the technique of fresco painting based on the use of "giornate" (day's work) had definitely replaced the a secco (on dry plaster) technique (or, in any case, the widespread use of background painting a secco) that advanced by "pontate" (sections).
The new procedure had resulted in abandoning the traditional, rigid graphic schemes, worked out over the centuries and codified in the treatises on Byzantine painting techniques. As a consequence, it became necessary to adjust the drawings of the images to be painted.
It was the duty of the maestro to invent and draw the images while the actual painting on the wall was generally left to his assistants with their various levels of specialization according to the experience each of them had acquired. Thus at Assisi the idea was born of a different organization of the work site, an organization that will find a novel development in the Scrovegni Chapel.

On this occasion, Giotto does the frescoes (according to Vasari) in the Loggia of Blessings in the Lateran Palaces. Those frescoes are lost today, and of that whole period there remains only the so-called Navicella in St. Peter's Basilica, but transposed into mosaics. In reality we have no certain information that Giotto had another sojourn in Rome except at a later date (1313) and in an entirely general way. That same fragment of wall painting at St. John Lateran traditionally interpreted as the opening of the Jubilee and thus dated 1300 could refer to Boniface VIII who took possession of the Lateran and so would be before 1297. The pope, however, is the same one who commissioned the Navicella from Giotto in 1300.

There was for sure a stop over in Rimini between Padua and Rome. What remains of it is the cross in the "Tempio Malatestiano" (St. Francis) while the frescoes in the church itself have perished. It is in this span of time that Giotto arrives in Padua called there, as always, by the Franciscans. (See the section "Giotto in Padua".)

1307-8 are the dates given for the decoration of the Cappella della Maddalena that Giotto carried out together with several helpers including the "Expressionist Maestro of Santa Chiara." Identified by Palmerino di Guido, who in a document of January 1309 returns some money in the name of Giotto.

In December 1311 and February 1312, Giotto is once again in Florence, occupied with business matters… Before 1312 he had made the Cross in Santa Maria Novella and a painted panel for San Domenico in Prato. In these years, he created the Maestà for the Church of Ognissanti, now in the Uffizi galleries; the Cross for San Felice in Piazza and the Raleigh polyptych, coming from the Peruzzi Chapel in Santa Croce, whose decorations date from those years. In 1314 he had recourse more than once to lawyers in order to collect money owed to him. Documentation in Florence goes blank until September 1318 when he endows his daughter Bice through his grown-up son Francesco, who was a painter too.

A fragment of these frescoes remains in the Fiumi collection in Assisi and the polyptych on the altar of the same basilica, now in the Pinacoteca, commissioned by Jacopo Stefaneschi.

A possible second sojourn in Padua has been taken into consideration, supported by Vasari's story that places it after 1316. It was in order to do frescoes in the Palazzo della Ragione (the cycle perished in a fire in 1420) as well as a lost chapel in the Basilica and a room in the Capitolo del Santo. Many scholars date both operations after the Scrovegni decorations (cf. Giotto in Padua). It has often been thought that the Crucifix in the Civic Museum was also done during this second sojourn, which Gnudi (1958) connects to the decision Enrico Scrovegni took in 1317 to provide an endowment for the celebration of the offices of the chapel. But more recently another scholar, Flores d'Arcais, has repeatedly claimed the Crucifix to be contemporary with the chapel's wall paintings.

In 1320, Giotto registers in the rolls of the Florentine doctors and chemists and in October names his lawyer. In January 1322, he purchases land at Colle di Vespignano, his hometown; in November 1325, he underwrites a bank loan; in January and in May 1326 he gives his daughter Chiara a dowry. These are years of intense activity that will see the creation of the frescoes in the Bardi Chapel at Santa Croce and the Franciscan polyptych that has been split up amongst the museums of Munich, New York and London, the Berenson Collection at Settignano and the Gardner Museum in Boston; the polyptych Goldman-Horne-Chaalis and the Dormitio Virginis in Berlin.

On January 20, 1330, the king names him as one of his familiars and in March 1332 makes him a gift of money for being "prothopictori familiari et fideli nostro"; the following month, Roberto d'Angiò gives him an annual pension for his services.
On behalf of the king, Giotto creates:
- a chapel in Castelnuovo (of which only fragments remain, attributed to Maso di Banco in the splay of the windows);
- King Uberto's Hall of Famous Men, as Ghiberti tells it. A Chapel in Santa Chiara (of which there remains only a fragment of the Grieving over the Christ's Body in the nuns' choir).
- A chapel in Castel dell'Ovo, again according Ghiberti, and of which no trace remains.

In April 1334 he is again in Florence where he is named maestro of the "Opera di San Reparata" and head engineer of the City of Florence; on July 18 of the same year he begins construction of the cathedral bell tower, the famous Giotto bell tower, and he delivers the drawings for the Stories of the Creation that are sculpted by Andrea Pisano (Ghiberti). He signs the polyptych of the Bologna Art Gallery and the one in the Baroncelli Chapel in Santa Croce. He begins the decoration of the "Cappella del Podestà" in the "Palazzo del Bargello" (Ghiberti) where there are badly damaged versions of the Last Judgment and Stories of the Maddalena, not attributed to his hand but to his workshop (D'Arcais).

In the destroyed "Azzone Visconti Palazzo", he decorates a hall with a "Worldly Glory".