The Irish were present among the early settlers in Western Virginia and came in particularly large numbers after the turn of the 19th century. They helped to build the early transportation network, beginning with the National Road, which arrived in Wheeling in 1818. An old Catholic cemetery in Triadelphia, Ohio County, has several tombstones dated 1819 from these early Irish.

With the National Road completed to Wheeling, great numbers of immigrants, including the Irish, found their way west to heavily industrialized Wheeling. The Irish also helped to build the Chesapeake & Ohio Canal along the Maryland side of the Potomac River from Washington to Cumberland, Maryland, beginning in 1828. Cholera produced mass graves along the canal route. The old Catholic cemetery at Shepherdstown holds some of these unnamed workers. The canal's great Paw Paw Tunnel, in Maryland across the river from Paw Paw, West Virginia, was dug by the Irish with picks, shovels, and bare hands. The tunnel opened in 1850 and finally completed the canal.

As the canal was being built, so too were the turnpikes, with the Irish heavily represented among the laborers. In the 1820s, the James River & Kanawha Turnpike ran from Lewisburg to Charleston. The Northwestern Turnpike was constructed in the 1830s from Winchester, Virginia, to Parkersburg. And in 1841, serious work commenced on the Staunton-Parkersburg Turnpike, which linked the Valley of Virginia to the Ohio River at its completion in 1847.

Overtaking the canal and turnpikes were the railroads. The first to come into Western Virginia was the Baltimore & Ohio, begun in Baltimore in 1828 and reaching Wheeling in January 1853. This 380-mile project employed thousands of men, many of them Irish. For three years Irish laborers built the tunnel at Tunnelton, reputedly the longest in the world, while living in the B&O labor camp at Greigsville outside Fairmont. In 1857, an auxiliary branch, the Northwestern Virginia Railroad, was finished from Grafton to Parkersburg. Later railroad lines using Irish labor included the Chesapeake & Ohio in the 1870s and the Norfolk & Western in the 1880s.

The large number of Irish workers in Western Virginia can be tied to the great out-migration of the Irish famine, 1845—50, when 1.2 million people left their homeland. The Irish workers could be an unruly bunch, often finding relief from their hard labors in saloons and continuing their homeland fights in the hills of Western Virginia.

Lewis County attracted a large Irish population. In the 1840s, a land company recruited Irish settlers from the nearby turnpike and B&O crews. Many Irish moved into the Sand Fork, Loveberry, and Leading Creek districts. In 1848, a Catholic Church was established at Sand Fork, and St. Patrick's Church at Weston was built. The Lewis County Irish, as so many others, were fervent Union supporters during the Civil War, and a great portion of Company B, 15th Virginia Infantry, under Michael Egan, were Irish recruits. One of the more revered Irish figures in Lewis County was Monsignor Thomas Quirk (died 1937), who ministered to the people for 50 years, often on horseback.

The Catholic Church was closely tied to the Irish of West Virginia. The first Catholic Church in West Virginia was established in Wheeling in 1822, composed largely of German and Irish parishioners. American Catholicism had a pronounced Irish look by the 1850s, and by the 1890s the hierarchy was almost entirely Irish. Thus the first bishop of the Diocese of Wheeling in 1850 was Richard V. Whelan. In Wheeling in 1853 when nativists adhering to the Know Nothing party threatened a papal diplomat visiting Wheeling, the bishop and his guest were protected by hundreds of armed Irish. Many of the clergy in the state had roots in Ireland, often recruited from All Hallows Missionary College in Dublin, and the backbone of the orders of religious women were German and Irish.

Many local names reflect the Irish presence in West Virginia, including Irish Ridge in Marshall County and St. Colman's Catholic Church on Sullivan's Knob at Irish Mountain in Raleigh County. The building of the C&O Railroad brought many Irish into the latter area, giving Hinton, the Summers county seat, a strong Irish presence and a St. Patrick's Church, one of six in the state. In Kanawha County at Coalburg stands a large Celtic cross, erected in 1912 by William S. Edwards to honor the Irish workers in his mines. Other Celtic crosses in cemeteries in Greenbrier County and elsewhere attest to an Irish presence.

The American Ancient Order of Hibernians, an Irish fraternal order founded in New York City in 1863, had two divisions in Wheeling in 1875 and one in Benwood. By 1884, the AOH had groups in Rowlesburg, Clarksburg, Parkersburg, Coal Valley, and Charleston. At its height in 1894, there were 647 men in 12 Hibernian divisions in West Virginia.

By the end of the 19th century, the Irish came to occupy positions of authority in West Virginia. Thomas O'Brien, a Wheeling citizen and Irish native, was elected state treasurer in 1880. Thomas Riley, whose father was Irish-born, was elected attorney general in 1892. The industrialist Michael Owens, born the son of Irish immigrants in Parkersburg, invented the bottle-making machine and was a founder of Libbey-Owens-Ford. U.S. Sen. John Kenna, one of two West Virginians whose statues are in the U.S. Capitol, had an Irish immigrant father. Bernard McDonough built a business empire from a Parkersburg base and later founded one of West Virginia's largest philanthropic foundations.