The son of a clergyman, he was born at Bridekirk near Carlisle. After a preliminary education he went in 1701 to the Queen's College, Oxford, taking his M.A. degree in 1709. He became fellow of his college in the next year, and in 1711 University Reader or Professor of Poetry. He did not take orders, but by a dispensation from the Crown was allowed to retain his fellowship until his marriage in 1726 in Dublin.

Tickell acquired the name ‘Whigissimus’, because of his close association with the Whig parliamentary party.

In 1717 he was appointed Under Secretary to Joseph Addison, Secretary of State. In 1724 Tickell was appointed secretary to the Lords Justices of Ireland a post which he retained until his death in 1740, at Bath.

Tickell owned house and small estate in Glasnevin on the banks of the River Tolka which later became the site of the Botanic Gardens. A double line of yew trees (known as Addison’s Walk) from Tickell’s garden is incorporated into the Gardens.

His grandson Richard Tickell became a playwright and married Mary Linley, of the Linley musical dynasty.

Tickell's success in literature, as in life, was largely due to the friendship of Joseph Addison, who procured for him (1717) an under-secretaryship of state, to the chagrin of Richard Steele, who from then on bore a grudge against Tickell. During the peace negotiations with France, Tickell published in 1713 the Prospect of Peace.

In 1715 he brought out a translation of the first book of the Iliad contemporaneously with Alexander Pope's version. Addison's reported description of Tickell's version as the best that ever was in any language roused the anger of Pope, who assumed that Addison was the author. Addison instructed Tickell to collect his works, which were printed in 1721 under Tickell's editorship.

Kensington Gardens (1722), Tickell's longest poem, is sometimes viewed as inflated and pedantic. It has been said that Tickell's poetic powers were awakened by his admiration for the person and genius of Addison, and undoubtedly his best work is the sincere and dignified elegy addressed to the Earl of Warwick on Addison's death. His ballad of Cohn and Mary was for a long time the most popular of his poems. Tickell contributed to The Spectator and The Guardian.