The house underwent important structural changes under the Fifth Earl. The long galleries of the West front were divided into smaller rooms. To the south, a suite of State Rooms known as front the George Rooms was started. However, the only room completed at the death of the Fift Earl was the First George Room.

On the ground floor, the Earl and Countess' apartments were created. With a common room at the centre of the West front, both apartments consisted of an anteroom, a bedroom, a dressing room and a closet, each one with a fireplace. This arrangement was also a metaphor of the progression of intimacy allowed to the visitor: the more a visitor could advance through the rooms, the closer the relationship with their host.

The Elizabethan gardens were transformed with canals, rising flights of terraces, ornamental fishponds, a maze, a vineyard and Queen Anne's Avenue, which is a mile long planting of twelve hundred lime trees.

The redecoration of the rooms revolved around the art purchased by the Fifth Earl and his wife during their tours through France and Italy. Among the items collected that can be seen today at Burghley are:

• the tapestries in the Queen Elizabeth Bedroom, ordered from the Gobelins factory, Paris;
• the early French floral marquetry furniture, which is now in the Blue Silk Room;
• many paintings, and
• pieces of Chinese porcelain.

They also patronised both English and continental craftsmen for the redecoration of the house. The craftsmen involved included:

• William Talman, for the structural changes;
• Jean Tijou, for the West Front iron gates;
• Edward Martens, for some of the ceilings;
• Grinling Gibbons, for some woodcarving;
• John Vanderbank, for the tapestries;
• Louis Laguerre, for the wall paintings in the Bow Room;
• Antonio Verrio for the George Rooms and part of the Great Staircase, and
• George London and Henry Wise, for the park and gardens.

When the Fifth Earl died, he was deeply in debt and all work stopped.