Even as Anne was laid to rest, a great Armada threatened England from across the Bay of Biscay. On 19 July 1588, about four weeks after Anne's interment, Spanish ships appeared off the coast of Cornwall and Devon.

The saga of the Spanish Armada is immense, surviving documentation vast. For our purposes it is enough to appreciate that the huge Spanish fleet was constantly harried by the English as it made its way along the south coast, prevented from landing at Portsmouth; it was then driven towards the sandbanks off Gravelines (near Calais) as it made a fruitless attempt to rendezvous with Parma, commander of Spanish land troops. A plan to tow barges full of Parma's men into the mouth of the Thames near Tilbury was thwarted not only by Parma's reluctance, but by the inherent difficulty of the enterprise, and by English fireships launched into the anchored Spanish fleet. By 29 July the Armada broke to the north, facing open seas, enormous distances, starvation, capture, and shipwreck, limping around Scotland and through the Irish Sea before finding safety in Spanish ports.

Evidence for Oxford's role in the battle of the Armada takes two separate forms: literary-historical reports and contemporary letters from Leicester. A modern recapitulation of the literary-historical thesis is given by Duff Hart-Davis, writing in 1988, the ‘Armada Year’: