In 1750-1753 Wood travelled to Syria with his friends the Oxford scholars James Dawkins (1722-1757) and John Bouverie and with the Italian architect Giovanni Battista Borra, who they had measure and draw the ancient ruins of Palmyra and Baalbek. The results were published in 1753 and 1757 in both English and French editions and were among the first systematic publications of ancient buildings. Both works were of great influence on neoclassical architecture in Britain and on the continent.
From 1753 to 1756, Wood was the companion of the young Duke of Bridgewater, the richest peer in England, in making the Grand Tour. In 1756 he was appointed Under Secretary to the Secretary of State for the Southern Department, who was initially Pitt the Elder. It was to Wood that Granville famously quoted an appropriate passage from Homer's Iliad as he signed the Treaty of Paris on his deathbed in 1763 (Wood published an essay on Homer in 1765, which stated that true knowledge can come only after one has had an opportunity to evaluate one's own society in relation to others). In 1764, following the instructions of Secretary of State Halifax, Wood acted under a general warrant to seize the papers of John Wilkes, who subsequently won damages of £1000 from him for trespass.
In 1761 Wood was elected Member of Parliament for Bridgewater's pocket borough of Brackley in Northamptonshire, which he continued to represent until his death. He was also Master of the Revels in Ireland, and at one point it was rumoured that he would be appointed Secretary to the Lord-Lieutenant of Ireland, but the Lord Lieutenant objected to Wood's "public and private character" as well as his "mean birth", and the appointment was never made.