He returned to England in the 1650s, where he was politically active in the administration of Oliver Cromwell as a Lord Commissioner of the Admiralty and member of Parliament.

Hopkins' will left substantial assets, in trust, for "Encouragement unto those forreign Plantations for the breeding up of Hopefull youth in the way of Learning both at ye Gramar School & Colledge for the publick Service of the Country in future times [and] for the upholding & promoting of the Kingdom of the Lord Jesus Christ in those parts of the earth."

[1] As a side effect of the early administration of the trust, the town of Hopkinton, Massachusetts, was named after him after Harvard College bought 12 500 acres of land there from the Hopkins endowment.

He may have benefited from connections with his uncle, Sir Henry Lello, who served for a time as English Ambassador to the Ottoman Empire, Warden of the Fleet Prison, and Keeper of the Palace of Westminster.

[5] He became involved in efforts to establish a colony on the shore of Long Island Sound that were under the aegis of the Lord Say and Sele and Baron Brooke.

Although Hopkins was not apparently a signer of the Saybrook Colony's patent, he was involved in procuring provisions for the colonization effort's inaugural expedition in 1635, headed by Lion Gardiner.

In the colony's first election in 1639 he became one of several Assistants to the General Court, along with George Wyllys, Thomas Welles, and John Webster.

He also oversaw the printing of the New Haven Colony's first laws, and served in the English Parliament during Cromwell's reign.