Enlisted in the Eastern Association army, Packer was a trusted lieutenant in Oliver Cromwell's cavalry regiment by 1644.
A religious radical, Packer clashed with Major-General Lawrence Crawford, who had him arrested for disobedience.
During the Rule of the Major-Generals (1655), he deputised for Charles Fleetwood as military governor of Hertfordshire and Oxfordshire.
Packer was elected to the Second Protectorate Parliament as MP for Woodstock, Oxfordshire, but he had grown discontented with Cromwell's policies.
Elected to the Third Protectorate Parliament in 1659, Packer delivered a speech in which he expressed his profound sense of betrayal by the Cromwellian régime and regret for some of his own actions as a major-general.