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Born in about 1729, Jacob Hiltzheimer left his native city of Mannheim, Germany, at the age of 19, embarking on the ship Edenburg for Philadelphia. Shortly after his arrival on September 5, 1748, Hiltzheimer was apprenticed to the silversmith John Nagle, but upon the termination of his term of service, he decided to leave the trade to take up farming and raising livestock. From the start of his new trade, Hiltzheimer took a particular interest in horses, and launched a prosperous livery stable where he raised and sold livestock, and he maintained a pasture for his stock at "Gravel Hill" on the outskirts of the city. His rising local prominence is suggested by advertisements in the Pennsylvania Gazette in which men interested in racing were required to register their horses with Hiltzheimer.

Although not a Quaker himself, Hiltzheimer married a Quaker woman Hannah Walker in 1761, and the two established themselves in a house on the corner of Seventh and High (Market) Streets, reportedly the same house where Thomas Jefferson later drafted the Declaration of Independence. He became a naturalized citizen on March 29, 1762, and from that point on, was an ardent patriot in a changing political climate. Hiltzheimer's great-grandson reported that during the French and Indian War, Hiltzheimer took part in a campaign to expel the French from the Ohio River and the lakes to the west, and during the Revolutionary War he served with the First Battalion of City Militia. A strong proponent of Independence, Hiltzheimer was entrusted by the Philadelphia Committee of Safety with taking firelocks out the city for safe keeping in 1776, and on August 13, 1777, he took the Oath of Allegiance confirming his patriotism. As a representative of the city of Philadelphia to the Quartermaster General, he was also given charge of procuring supplies, including horses, for the Continental Army.

In 1784, Hiltzheimer began a successful political career with an appointment as Street Commissioner, and in 1787, he was elected as a representative to the Pennsylvania Assembly, serving for 11 consecutive years. He sat on several committees in the Assembly, chairing the Committee of Claims, and maintained a full slate of civic involvements, including the German Society of Pennsylvania for which he was elected Vice-President, the Society for the Promotion of Domestic Manufactures, the Society for Promoting Agriculture, the Republican Society, and the Fire Department.

Hiltzheimer's wife died on March 9, 1790, after a "long and painful illness," but Jacob's end would come far more swiftly. Having survived the great yellow fever epidemic of 1793, Hiltzheimer sat down on September 4, 1798, to record 66 deaths in his diary. On the next day, however, he became infected himself, succumbing to the disease on 14 September 1798.