Transcriptional enhancers activate gene expression over large genomic distances, yet how specific enhancer-gene pairing is established remains mostly unclear. The loop extrusion model, in which the cohesin complex actively extrudes DNA until stalled by convergently oriented CTCF sites, has been proposed as a widespread mediator of enhancer-gene interactions. However, few nuclear factors besides CTCF/cohesin have been studied for a direct role in physically connecting regulatory elements. We show via acute degradation experiments that the transcription co-factor, LDB1 directly and broadly promotes connectivity among regulatory elements. Most LDB1-mediated contacts, even those spanning hundreds of kb, are maintained in the absence of CTCF or cohesin as determined using multiple degron systems. Cohesin-driven loop extrusion does not stall at LDB1-occupied sites but aids the formation of a subset of LDB1-anchored loops. Tri-C and Region Capture Micro-C reveal that LDB1 organizes multi-enhancer networks to activate transcription. To test whether loop extrusion is required for the de novo establishment of LDB1-mediated contacts, we explored the formation of chromatin folding patterns at the mitosis-to-G1-phase transition upon acute loss of the loop extrusion-promoting factor NIPBL. NIPBL depletion primarily impaired the formation of cohesin-mediated structural loops with NIPBL dependence being proportional to loop length. In contrast, the majority of CRE loops—including those dependent on LDB1—were established independently of loop extrusion regardless of length. Accordingly, transcription of most genes was activated normally in the absence of NIPBL. Notably, LDB1-dependent CRE loops formed without NIPBL, even when residing within TADs that are lost upon NIPBL depletion. In sum, LDB1 emerges as a direct driver of regulatory network inter-connectivity