Humphrey was one of several earls and barons under Edward I who laid siege to Caerlaverock Castle. Being very close to the border with England, it had to be defended several times against English forces. One such occasion was the Siege of Caerlaverock of 1300 by Edward I of England who had eighty seven of the most illustrious Barons of England in his host, including knights of Bretagne and Lorraine. The Maxwells, under their gallant chief, made a vigorous defence, showering upon their assailants such heavy missiles that they retired time and again; but in the end the garrison were compelled to surrender, when it was found that there were only sixty men all told, and that they had defied the whole English army for a considerable period. In recent years, Historic Scotland has organised re-enactments of the Siege.

Humphrey de Bohun received many of Robert Bruce's forfeited properties. It is unknown whether Humphrey was a long-time friend or enemy of Robert Bruce, but they were nearly the same age and the lands of the two families in Essex and Middlesex lay very close to each other. After Bruce's self-exile, Humphrey took Lochmaben, and Edward I awarded him Annandale and the castle. During this period of chaos, when Bruce's queen, Elizabeth de Burgh, daughter of the Earl of Ulster, was captured by Edward I and taken prisoner, Hereford and his wife Elizabeth became her custodians. Lochmaben was from time to time retaken by the Scots but remained in the Bohun family for many years, in the hands of Humphrey's son William, Earl of Northampton, who held and defended it until his death in 1360.