On the south exterior of the nave is a blocked, medieval doorway, said to be late-12th century. In 1717, it was declared that there was no maintenance for a curate at Clifton Chapel, or any ecclesiastical services performed there. Between 1736 and 1821, the burial ground had ceased to be used and the building was in a state of disrepair. The church was subsequently restored in 1858 and rebuilt in 1900.

Domesday Book did not cover this part of England, but there is evidence that there was a religious site in Clifton at least as early as the 10th century, as part of a decorated cross shaft thought to date from the 10th century was found in 1900 built into the church. King William II went into Cumbria in 1092, when he claimed Carlisle and ordered that a castle be built there. It is not certain when Ranulf Meschin was entrusted with Cumbria, but it appears to have been about 1106 by King Henry I. In 1122 Ranulf, having succeeded to the earldom of Chester, surrendered Cumbria to Henry I, under the condition that the feoffees should hold their land in capite of the crown. King Henry, in turn, granted Allerdale above Derwent (i.e. Allerdale south of the Derwent) to William Meschin, brother of Ranulf. This new barony of Copeland became known as the barony of Egremont. William sub-granted a section of this, between the rivers Cocker and Derwent, to Waldeve lord of Allerdale below Derwent (i.e. Allerdale north of the Derwent), son of Gospatric. It is the area between the two rivers that became the Honour of Cockermouth, which contained the vills of Brigham, Easlesfield, Dean (with Branthwaite), Greysouthen, and the two Cliftons (with Stainburn), which lay within the diocese of York. It continued to be dependent on the barony of Egremont and not on Allerdale below Derwent. In 1136, King David I of Scotland recovered this part of Cumbria, which remained under Scottish control until 1157, at which time it was taken back by King Henry II of England. St Luke’s Church is sited about half-way between Cockermouth and Workington, along the main road connecting them. During the medieval period, St Luke’s appears to have been the church mentioned simply as the chapel (capella) of Clifton. Clifton, itself, is divided into two sections: Great Clifton (Clifton Magna or Kirk Clifton) and Little Clifton (Clifton Parva). Ecclesiastically, Great Clifton and Little Clifton formed one parish. St Luke’s Church falls between the two parts, a bit closer to the centre of Little Clifton. Sometime between 1160 and 1181, the archbishop of York, Roger of Pont-l’Eveque, confirmed to the priory of St Bees lands belonging to them which included the chapel of Clifton. Waltheof, son of Thomas clerico of Dean (probably the same referred to later as T. rector ecclesie de Dene), was given the chapel at some point between 1178 and 1184. Under Thomas, rector of Dean, the inhabitants of Clifton were induced to be buried in the churchyard at Dean, but the rector of Workington appealed, as the chapel of Clifton was a dependent of the parish of Workington. This dispute finally came to an end when in 1219 Pope Honorius III declared that the church at Dean was to cease such action. After Waldeve died, the Honour of Cockermouth had passed to his son Alan, who died in or about 1150 without a male heir. Descent then passed to William fitz Duncan (died about 1160), son of Etheldreda (who appears to have been the sister of the earlier Gospatric), and closest male relative to Alan. He was married to the daughter and heir of William Meschin. On William fitz Duncan's death, his widow Alicia continued control of this domain. Dying without a male heir, King Henry II, made a fresh grant between her three daughters, who became King Henry’s wards with respect to Allerdale. Alicia, the youngest daughter, received Allerdale and the Honour of Cockermouth, along with her first husband, Gilbert Pipard (d. 1191-2), and then with her second husband, Robert de Curtenai (d. 1209-10). She was still in possession of Allerdale and the Honour of Cockermouth in 1212, but died in or by 1215, leaving no heir. After Alicia's death, her estates passed through her elder sisters, Cecila and Amabilla. In 1215, King John awarded the Honour of Cockermouth to William de Fortiibus, Earl of Albemarle, who was married to Hawise, daughter of Alicia's sister Cicely. 'De Clifton' family members, who presumably held the manor of Clifton, can be found in charters as early as the late-12th century, most commonly as witnesses to charters in the Register of the Priory of St Bees. They continued to appear prominantly throughout much of the 13th century.

The dedication of the church to St Luke is relatively modern. During the medieval period, no dedication is recorded. Although the church is located at the outer edge of Little Clifton, the church is sometimes referred to as that of Great Clifton. The manor of Clifton consisted of the two Cliftons, and the church between them appears to have served both places.

The doorway is often referred to as the 'Norman doorway'. Hyde and Pevsner say the doorway is 'Late Norman', while Bulmer says the church dated from the 'reign of the first of the Plantagenets'. The use of dogtooth suggests the doorway cannot be earlier than this. The historical documents, which highlight interests in the chapel at this time, would seem to support a likely date in the later-12th or early-13th century.

The section of cross found in 1900 built into the fabric is now displayed inside the church. The Victorian County History (vol. 1, p. 275) states that it was found in the foundations, while Lidbetter says a doorway was discovered during the demolition of the church walls in 1900 and the cross shaft was found 'serving as the lintel'.