Le Loutre became the leader of the French forces and the Acadian and Mi'kmaq militias during King George's War and Father Le Loutre's War in the eighteenth-century struggle for power between the French, Acadians, and Miꞌkmaq against the British over Acadia (present-day Nova Scotia and New Brunswick).

The British were settled mostly in the capital Annapolis Royal, while Acadians and the native Mi'kmaq occupied the rest of the region.

By the end of the war, most British officials who had been sympathetic toward the Acadians concluded that they and Le Loutre were supportive of the French position.

The first Siege of Fort Anne was made in July 1744 but ended after four days due to the failure of French naval support to arrive.

In the late-spring/early summer Nova Scotia Lieutenant-Governor Paul Mascarene wrote to Massachusetts governor William Shirley requesting military aid.

After the two attacks on Annapolis Royal, Massachusetts Governor William Shirley put a bounty on the Passamaquoddy, Mi’kmaq and Maliseet.

After the capture of Louisberg, the British attempted to lure La Loutre to come there for his own safety, but he chose to go to Québec to confer with the authorities.

Yet another attempt at Annapolis Royal was organized with Jean-Baptiste Nicolas Roch de Ramezay and the ill-fated Duc d'Anville Expedition in 1746.

With Louisbourg captured by the British, Le Loutre became the liaison between the Acadian settlers and French expeditions by land and sea.

He had to coordinate the operations of the naval force with those of the army of Ramezay, sent to retake Acadia by capturing Annapolis Royal early in June 1746.

Ramezay and his detachment arrived at Beaubassin (near present-day Amherst, Nova Scotia) in July, when only two frigates of the French squadron had reached Baie de Chibouctou.

Without seeking the agreement of the two captains, Le Loutre wrote to Ramezay suggesting an attack be made on Annapolis Royal without the full expedition; but his advice was not acted upon.

Charles Lawrence first tried to establish control over Beauséjour and then at Beaubassin early in 1750, but his forces were repelled by Le Loutre, the Mi'kmaq, and Acadians.

Le Loutre saved the bell from Notre Dame d'Assumption Church in Beaubassin and put it in the cathedral he had built beside Fort Beauséjour.

Often aboriginal allies fought on their own while the imperial powers tried to conceal their involvement in such initiatives, to prevent igniting large-scale warfare between England and France.

By the time Cornwallis had arrived in Halifax, there was a long history of conflict between the Wabanaki Confederacy (which included the Mi'kmaq) and the British.

On September 30, 1749 when a Mi'kmaq force from Chignecto raided Major Ezekiel Gilman's sawmill at present-day Dartmouth, Nova Scotia, killing four workers and wounding two.

Cornwallis strongly refused their request and directed them that if they left, they could not take any belongings, and warned them that if they went to the area north of the Missaguash River they would still be in English territory and still be British subjects.

The priest tried to establish new communities, but found it difficult to supply the new settlers, the Mi'qmaq, and the garrisons at Fort Beauséjour and Île Saint-Jean (now Prince Edward Island) with food and other necessities.

Finding the living conditions deplorable at New Brunswick and Prince Edward Island, he made repeated appeals in 1752 for aid from the authorities in Quebec.

Protecting low-lying lands from the tides would enable their use as pasture for cattle and development with cultivation for crops, so the Acadians could escape the risk of starvation.

In 1754 Bishop Henri-Marie Dubreil de Pontbriand of Quebec appointed Le Loutre vicar-general of Acadia.

Historian Micheline Johnson has described him as "the soul of the Acadian resistance,"[14] and he enjoyed wide support amongst French-Canadian priest-historians of the 19th and 20th centuries.