A successful soldier from a military family, in 1212, John was chosen by Emperor Theodore I Laskaris as husband for his daughter Eirene Laskarina and as heir to the throne. This arrangement excluded members of the Laskarid family from the succession, and when John III Doukas Vatatzes became emperor in mid-December 1221, he had to suppress opposition to his rule. The struggle ended with a battle in 1224, in which his opponents were defeated in spite of the support they had acquired from the Latin Empire of Constantinople. John III's victory led to territorial concessions by the Latin Empire in 1225, but was followed by John's incursion into Europe, where he seized Adrianople.
John III's possession of Adrianople was terminated by Theodore Komnenos Doukas of Epirus and Thessalonica, who drove the Nicaean garrison out of Adrianople and annexed much of Thrace in 1227. The elimination of Theodore by Ivan Asen II of Bulgaria in 1230 put an end to the danger posed by Thessalonica, and John III made an alliance with Bulgaria against the Latin Empire. In 1235 this alliance resulted in the restoration of the Bulgarian patriarchate and the marriage between Elena of Bulgaria and Theodore II, respectively Ivan Asen II's daughter and John III's son. In the same year the Bulgarians and Nicaeans campaigned against the Latin Empire, and in 1236, they attempted a siege of Constantinople. Subsequently, Ivan Asen II adopted an ambivalent policy, effectively becoming neutral, and leaving John III to his own devices.
In spite of some reverses against the Latin Empire in 1240, John III was able to take advantage of Ivan Asen II's death in 1241 to impose his own suzerainty over Thessalonica (in 1242), and later to annex this city, as well as much of Bulgarian Thrace in 1246. Immediately afterwards, John III was able to establish an effective stranglehold on Constantinople in 1247. The last years of his reign saw the extension of Nicaean authority far to the west, where John III attempted to contain the expansion of Epirus.
John III Doukas Vatatzes was a successful ruler who laid the groundwork for Nicaea's recovery of Constantinople. He was successful in maintaining generally peaceful relations with his most powerful neighbors, Bulgaria and the Sultanate of Rüm, and his network of diplomatic relations extended to the Holy Roman Empire and the Papacy, while his armed forces included Frankish mercenaries.
John III effected Nicaean expansion into Europe, where by the end of his reign he had annexed his former rival Thessalonica and had expanded at the expense of Bulgaria and Epirus. He also expanded Nicaean control over much of the Aegean and annexed the important island of Rhodes.
Moreover, John III is credited with carefully developing the internal prosperity and economy of his realm, encouraging justice and charity. In spite of his epilepsy, John III had provided active leadership in both peace and war. At some point after his death, John III was canonized as a saint, under the name John the Merciful.