Custis was the son of(ca. 1629–1696) and the first of his three wives, Elizabeth Robinson Eyer (or Eyre) Custis. He was born in Northampton County about 1654, and although information about his early years is limited, he apparently received a good education and developed the sense of noblesse oblige expected of the son of a . By mid-1678 Custis had married Margaret Michael. They had two daughters and seven sons. The eldest son, also named (1678–1749), later served on the governor’s Council. Custis’s wife died after the birth of their second daughter, whom he named Sorrowful Margaret Custis. By 1691 he had married Sarah Littleton Michael, the widow of his first wife’s eldest brother. They had no children.
Sometimes referred to as John Custis, of Wilsonia (his Northampton County plantation), he was one of the principal planters and wealthiest men on the Eastern Shore, where he owned thousands of acres of land and a large number of enslaved laborers. His public career began on July 29, 1675, when his father, then the coroner of Northampton County, made him deputy coroner. Custis replaced his father as a justice of the peace in the summer of 1677 when his father was elevated to the governor’s Council. He served as sheriff of the county in 1682, 1684, and 1688. In the summer of 1691 Custis became a member of the new Hungars Parishand insisted on ordering the first and finest pew when the new church was erected. He also advanced from captain to colonel in the county militia. Evidence suggests that he often appeared in court in the role of an attorney, employing his considerable ability and self-confidence in the interest of his clients.
In 1684 Custis wasto represent Northampton County in the House of Burgesses, but he was disqualified after being chosen sheriff of the county. In the election held to fill the open seat in the House, voters again selected Custis. Records for the 1685 sessions are not extant, but he was returned again in 1686. During the assembly session that met in the autumn of that year he emerged as a respected member of the House and was appointed ranking member of the Committee of Propositions and Grievances. After several years out of the assembly, Custis was returned in the spring of 1693, resumed his influential seat on the Committee for Propositions and Grievances, and joined the Committee for Elections and Privileges. After less than a month, illness forced him to return home, and during the brief session of the assembly held that autumn he chaired the Committee for Elections and Privileges before leaving early because of illness in his family. Elected again in 1695, Custis missed the assembly session that met in the spring of the following year but in the autumn of 1696 once again became chair of the Committee for Elections and Privileges and retained his high-ranking seat on Propositions and Grievances. He missed the session of October 1697 and most of the brief session in October of the following year, but during the long session that began in April 1699 he was once again one of the most active members and kept his two prized committee seats. He also chaired the committee of burgesses that reported to the governor and Council on the choice of Middle Plantation for the new capital of the colony.
On the recommendation of Governor, the king appointed Custis to the governor’s Council on December 26, 1699. Custis took his seat on July 9, 1700, and attended the Council for the last recorded time on April 30, 1713. His tenure spanned two politically contentious periods, the final years of Nicholson’s second administration and the first years of the administration of Lieutenant Governor , as well as the initial construction of the capitol and governor’s mansion at Middle Plantation, which became Williamsburg.
Custis wrote his will in December 1708. He provided for his wife and children as well as friends and relatives and in the process itemized many valuable items of silver, almost 7,000 acres of land, and more than thirty slaves and half a dozen Indians whose legal status is not clear. On May 12, 1705, the Council had distributed several Nanzatico children to responsible planters in order to protect them from presumed dangers from other Indians, with an order that they be held as servants until the age of twenty-four and then freed. Unless Custis changed the name of the one infant girl assigned to him, he did not mention her in his will. Declining health and gout forced Custis to remain at home and miss some meetings of the Council. In a letter to his namesake son in June 1713 he mentioned crippled hands, which might have been the consequence of gout or arthritis. Custis died in Northampton County on January 26, 1714, and was buried on his plantation at Wilsonia Neck.