The traceable story begins in the 6th century with Saint Jarlath. According to the Life of Brendan of Clonfert, the older monk told Jarlath to build a new chariot, set out, and stop where the two hind shafts broke. They broke at Tuam. Jarlath founded a monastery there - the historians caution that the broken wheel is folklore, but the monastery is real - and the town grew up around it, keeping the broken wheel as its heraldic device. In 1049 Aedh O'Connor defeated the King of Iar Connacht in battle, built a castle at Tuam, and made it the principal stronghold of his dynasty. A century later his descendant Turlough O'Connor reigned as High King of Ireland from 1106 to 1156, sponsoring the great works of 12th-century Celtic art - the High Cross of Tuam, the Cross of Cong - that still survive. His son Ruaidri became the last native High King of Ireland.

Tuam has two cathedrals, and the fact says almost everything about post-Reformation Irish history. The Cathedral of the Assumption is the Catholic seat of the Archdiocese of Tuam, an enormous diocese stretching from the Atlantic at Achill Island to the River Shannon. St Mary's Cathedral, on a separate site, is the Church of Ireland cathedral, built between 1861 and 1878 around the surviving 12th-century chancel arch of the original O'Connor cathedral. The two stand within easy walking distance of each other. The High Cross of Tuam, raised by Turlough O'Connor in the 12th century to mark the founding of the first cathedral, became the subject of an inter-denominational tussle in the 1850s, and was eventually placed halfway between the two churches before being moved indoors in 1992 to protect it from the weather.

From the late 19th century the railway and the sugar beet trade gave Tuam an industrial base. The Irish Sugar Factory off the Ballygaddy Road processed beet brought in by rail until the closures of the late 20th century. In the 1960s Tuam was known as the Showband Capital of Ireland, home to the Johnny Flynn Showband and others who toured the dance halls of the era. The compilation Songs from the Broken Wheel collected over fifty original tracks by Tuam musicians in 2009. And from Tuam came The Saw Doctors, whose songs about the N17, the Bishop, and the town's small triumphs and disappointments became a soundtrack for a generation of Irish people. The town is referenced in The Rocky Road to Dublin, a song about a man leaving Tuam for Liverpool. Tuam has always been somewhere people leave from, and somewhere they come back to.

Tuam Stars, founded in 1888, is the local Gaelic football club and one of Galway's most successful, with seven consecutive County Championship titles from 1954 to 1960. Sean Purcell and Frank Stockwell - widely regarded as one of the greatest forward partnerships in the history of the sport - both wore the Tuam colours during that run. St Jarlath's College in the town has won the Hogan Cup (the national second-level schools championship) twelve times since 1946, a record. Tuam Stadium, opened in 1950 by the Archbishop of Tuam, was for decades the home of Galway football, hosting Connacht senior finals and one of the great rivalries in Irish provincial sport.

From 1925 until 1961, a building on the northwest edge of Tuam operated as a Mother and Baby Home run by the Bon Secours sisters. Until the early 20th century it had been a workhouse - a Famine-era institution for the destitute. Local historian Catherine Corless began researching the Home in the early 2010s. By 2014 she had documented the deaths of 796 children there with no corresponding burial records. The story broke internationally. Exploratory excavations in 2016 and 2017 found significant human remains, infants and small children, interred in a disused underground structure with twenty chambers, related to the treatment of sewage. Most burials dated from the 1950s. The Mother and Baby Homes Commission of Investigation reported in January 2021 that around 9,000 children had died across 18 such institutions in Ireland between 1922 and 1998. Full forensic excavation of the Tuam site began on 14 July 2025, expected to take roughly two years. It is the largest reckoning of its kind ever undertaken in Ireland.

Today Tuam is the second-largest settlement in County Galway, a market town of around 9,000 people at the centre of north Galway. Valeo Vision Systems, the largest employer, has over a thousand people on site. The M17 motorway opened in September 2017, freeing the town from the worst of the traffic that used to crawl through its centre. The Mill Museum off Shop Street - an undershot waterwheel mill in operation until 1964 - is the only preserved corn mill in the west of Ireland. The Tuam Herald, founded in 1837, is County Galway's oldest newspaper. The Old Tuam Society, founded in 1942, publishes the journal JOTS. Markets still happen at the plaza in front of the shopping centre on the last Saturday of each month. The country around the town remains intensely farmed, intensely catholic, and intensely involved in its own past.